What is the Ketogenic Diet?
The ketogenic diet (KD) is a high-fat, adequate-protein, low-carbohydrate diet. When glucose intake is reduced, the body shifts to using fat as its primary energy source, a process known as ketogenesis. During ketogenesis, the liver breaks down fatty acid
to produce ketone bodies, primarily acetoacetate, acetone, and β-hydroxybutyrate. These ketone bodies become the primary energy source for the central nervous system.
Potential of the KD in Treating Psychiatric Disorders
While the KD is an established non-pharmacological treatment for epilepsy, emerging research suggests that it may also hold therapeutic potential for individuals with serious mental illnesses (SMI) such as:
Bipolar Disorder
Major Depressive Disorder
Schizophrenia
Several underlying mechanisms in the pathophysiology of mental illness may be influenced by the KD. For example, the KD has been shown to:
Alleviate inflammation and oxidative stress: Both of these are implicated in various psychiatric disorders
Modulate the gut microbiota community: Imbalances in gut bacteria have been linked to mental health conditions.
Improve metabolic health markers: Individuals with SMI often experience metabolic abnormalities.
Research Findings
Preliminary research suggests a potential therapeutic effect of the KD on SMI, including:
Weight reduction
Improvements in carbohydrate and lipid metabolism
Reduction in disease-related symptoms
Increased energy and quality of life
Potential changes in pharmacotherapy (reduction in medication number or dosage)
However, it's essential to note that much of the existing research on the KD's effects on SMI is based on:
Case studies: These offer limited generalizability.
Small-scale clinical trials: Larger studies are needed to confirm preliminary findings.
Some notable findings from studies on the KD's impact on specific mental illnesses include:
Schizophrenia:
A pilot study showed that patients with schizophrenia on a KD for four months experienced:
Significant weight loss (12%)
Improvements in metabolic health
A 32% reduction in Brief Psychiatric Rating Scale scores
Improved overall clinical global impression severity (31%)
Animal studies also indicate that the KD can:
Regulate abnormal behaviors in a mouse model of schizophrenia
Prevent sensory gating deficiencies
Protect against antipsychotic-induced hyperglycemia
Depression:
A case study found that a 65-year-old woman with major depressive disorder experienced:
Remission of depressive symptoms after following a KD for three months
Reduction in medication usage
Improvements in weight, blood pressure, blood glucose, and triglycerides
Animal research indicates that the KD may:
Have antidepressant-like effects
Reduce susceptibility to depressive and anxiety states
Bipolar Disorder:
A pilot study involving 16 individuals with bipolar disorder on a KD for four months showed:
Increased life satisfaction
Enhanced sleep quality
Improvements in the severity of mental illness for 69% of participants
Case studies and online forum analyses also suggest potential benefits of the KD for bipolar disorder, such as:
Mood stabilization
Reduction in depressive episodes
Improved cognitive function and concentration
Important Considerations for Psychiatrists
Initiating the KD for patients with SMI should always be done with caution and under the supervision of a physician and a registered dietitian. This is due to:
Potential side effects of the diet: These may include headache, fatigue, constipation, and electrolyte imbalances, though often subside after the initial weeks.
Potential for exacerbating adverse effects of pharmacotherapy: The KD can interact with certain medications
Key interactions between ketogenic diet and medications
Lithium:
Initial diuretic effect from ketosis causes fluid shifts
Hyponatremia elevates lithium
Because lithium competes with sodium for renal resorption
Lithium levels can increase 20-35% in the first 2-4 weeks of keto
Management:
More frequent lithium level monitoring first month
Maintaining adequate hydration/electrolytes (LMNT or Re-Lyte)
May need lithium dose reduction
Gradual rather than abrupt diet transition
Valproic Acid:
VPA competes with ketones for protein binding
May increase free drug levels without affecting total VPA as routinely reported
Consider checking free VPA level
Warfarin:
Altered absorption due to high fat intake
Changes in vitamin K intake affect INR
Requires closer monitoring
Diuretics:
Increased risk of dehydration/electrolyte imbalance
Enhanced natriuretic effect
Psychiatrists should consider the following when deciding on the suitability of the KD for a patient:
Patient's individual characteristics: Factors such as age, overall health status, lifestyle, and medication regimen should be taken into account.
Potential risks and benefits: A thorough discussion of these should be conducted with the patient.
Need for ongoing monitoring: Regular check-ups are crucial to assess the diet's impact on both mental and physical health.
Ongoing Research
A significant number of clinical trials are currently underway to further investigate the KD's impact on psychiatric disorders. These studies are crucial for:
Confirming the preliminary findings from smaller studies.
Establishing the long-term efficacy and safety of the KD for SMI.
Identifying the optimal protocols for implementing the KD in clinical practice.
Conclusion
The KD presents a promising avenue for adjunctive treatment in individuals with SMI. Early research suggests potential benefits for various mental health conditions, particularly in improving metabolic health and reducing symptom severity. However, larger-scale, long-term studies are needed to confirm these findings and guide clinical practice. Psychiatrists should exercise caution and collaborate with dietitians to ensure the safe and effective implementation of the KD for their patients.
Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., ... & Saslow, L. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry research, 335, 115866.
Rog, J., Wingralek, Z., Nowak, K., Grudzień, M., Grunwald, A., Banaszek, A., & Karakula-Juchnowicz, H. (2024). The Potential Role of the Ketogenic Diet in Serious Mental Illness: Current Evidence, Safety, and Practical Advice. Journal of Clinical Medicine, 13(10), 2819.
Mentzelou, M., Dakanalis, A., Vasios, G. K., Gialeli, M., Papadopoulou, S. K., & Giaginis, C. (2023). The relationship of ketogenic diet with neurodegenerative and psychiatric diseases: a scoping review from basic research to clinical practice. Nutrients, 15(10), 2270.
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